Prion Propagation: The Role of Protein Dynamics

Pezza, John A.; Serio, Tricia R.

doi:10.4161/pri.1.1.3992

Cited by 24 publications

(27 citation statements)

References 140 publications

(171 reference statements)

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“…Prion aggregates result from the specific conversion of soluble proteins into ordered amyloids. Their propagation involves several steps, starting from prion fibril growth via incorporation of soluble monomers, followed by the generation of seed templates (propagons) by fibril fragmentation and their delivery to daughter cells during cell division (Pezza and Serio, 2007;Shorter and Lindquist, 2005;Tuite and Serio, 2010;Wickner et al, 2009) (Fig. 2).…”

Section: Formation and Propagation Of Yeast Prion Aggregatesmentioning

confidence: 99%

Chaperone networks in protein disaggregation and prion propagation

Winkler

Tyedmers

Bukau

et al. 2012

Journal of Structural Biology

122

127

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Section: Formation and Propagation Of Yeast Prion Aggregatesmentioning

confidence: 99%

Chaperone networks in protein disaggregation and prion propagation

Winkler

Tyedmers

Bukau

et al. 2012

Journal of Structural Biology

122

127

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“…First, empirical and theoretical studies indicate that the interaction of membrane proteins -in particular, the stability of homo-and hetero-dimers -is affected by the extent of their dilution in lipid bilayers [81,82]. Second, as prions demonstrate, proteins can serve as templates for their own self-replication [83][84][85]. Third, experiments show that membrane proteins selectively recruit other proteins to Ras nanoclusters and adjust their orientation to maintain intracellular signaling [86][87][88][89].…”

Section: Some Membrane Patterns Can Be Inherited Apart From the Dnamentioning

confidence: 99%

The Membrane Code: A Carrier of Essential Biological Information That Is Not Specified by DNA and Is Inherited Apart from It

Wells¹

2013

Biological Information

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According to the most widely held modern version of Darwin's theory, DNA mutations can supply raw materials for morphological evolution because they alter a genetic program that controls embryo development. Yet a genetic program is not sufficient for embryogenesis: biological information outside of DNA is needed to specify the body plan of the embryo and much of its subsequent development. Some of that information is in cell membrane patterns, which contain a two-dimensional code mediated by proteins and carbohydrates. These molecules specify targets for morphogenetic determinants in the cytoplasm, generate endogenous electric fields that provide spatial coordinates for embryo development, regulate intracellular signaling, and participate in cell-cell interactions. Although the individual membrane molecules are at least partly specified by DNA sequences, their two-dimensional patterns are not. Furthermore, membrane patterns can be inherited independently of the DNA. I review some of the evidence for the membrane code and argue that it has important implications for modern evolutionary theory.

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“…Second, they are continually regenerated to create new surfaces for efficient conversion (Ness et al, 2002;Cox et al, 2003;Satpute-Krishnan et al, 2007), and third, they are partitioned to daughter cells where they continue the cycle and allow inheritance of the associated phenotype (Cox et al, 2003;Satpute-Krishnan et al, 2007). Thus, the strong link between protein state and phenotype that allows proteins to act as epigenetic elements is established and maintained through a multistep pathway of protein dynamics (Pezza and Serio, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…© 2009 by The American Society for Cell Biology maintained through a multistep pathway of protein dynamics (Pezza and Serio, 2007). Much of our mechanistic understanding of the Sup35/ [PSI ϩ ] in vivo prion cycle has its origins in a variety of genetic screens, which identified key modulators of this process.…”

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confidence: 99%

The NatA Acetyltransferase Couples Sup35 Prion Complexes to the [PSI⁺] Phenotype

Pezza

Langseth

Yamamoto

et al. 2009

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Protein-only (prion) epigenetic elements confer unique phenotypes by adopting alternate conformations that specify new traits. Given the conformational flexibility of prion proteins, protein-only inheritance requires efficient self-replication of the underlying conformation. To explore the cellular regulation of conformational self-replication and its phenotypic effects, we analyzed genetic interactions between [PSI ؉ ], a prion form of the S. cerevisiae Sup35 protein (Sup35 [PSI ؉ ] ), and the three N ␣ -acetyltransferases, NatA, NatB, and NatC, which collectively modify ϳ50% of yeast proteins. Although prion propagation proceeds normally in the absence of NatB or NatC, the [PSI ؉ ] phenotype is reversed in strains lacking NatA. Despite this change in phenotype, [PSI ؉ ] NatA mutants continue to propagate heritable Sup35 [PSI ؉ ] . This uncoupling of protein state and phenotype does not arise through a decrease in the number or activity of prion templates (propagons) or through an increase in soluble Sup35. Rather, NatA null strains are specifically impaired in establishing the translation termination defect that normally accompanies Sup35 incorporation into prion complexes. The NatA effect cannot be explained by the modification of known components of the [PSI ؉ ] prion cycle including Sup35; thus, novel acetylated cellular factors must act to establish and maintain the tight link between Sup35 [PSI ؉ ] complexes and their phenotypic effects. INTRODUCTIONThe transmission of phenotypes from one individual to another is a fundamental process in biology. Much of our understanding of these events arises from decades of study on nucleic acid metabolism, but new traits may also be passed between individuals without changes in nucleic acid content through a number of epigenetic mechanisms. One particularly intriguing example of such a process is the prion phenomenon, in which the activity of a protein is altered in a heritable way to transmit a new phenotype. How is such a feat accomplished? In 1967, Griffith proposed that some proteins, now known as prions (Prusiner, 1982), can adopt more than one stable form in vivo (Griffith, 1967). Since a protein's structure determines its function, two cells containing the same protein but in diffrent physical states will have distinct phenotypes. This protein-based process has been linked to a number of previously inexplicable events, including the development and spread of the transmissible spongiform encephalopathies in mammals (Prusiner, 1982) and the non-Mendelian inheritance of some traits in fungi (Wickner, 1994).Protein-based traits can only become transmissible, however, if the inherent structural flexibility of prion proteins can be constrained by regulatory mechanisms to create an epigenetic element. For example, if each newly synthesized prion polypeptide chain independently folded to a unique form, all cells would display the same phenotype, which would reflect the average of the accessible states. The appearance of distinct protein-based phenotypes suggests that ...

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Prion Propagation: The Role of Protein Dynamics

Cited by 24 publications

References 140 publications

Chaperone networks in protein disaggregation and prion propagation

Chaperone networks in protein disaggregation and prion propagation

The Membrane Code: A Carrier of Essential Biological Information That Is Not Specified by DNA and Is Inherited Apart from It

The NatA Acetyltransferase Couples Sup35 Prion Complexes to the [PSI⁺] Phenotype

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Prion Propagation: The Role of Protein Dynamics

Cited by 24 publications

References 140 publications

Chaperone networks in protein disaggregation and prion propagation

Chaperone networks in protein disaggregation and prion propagation

The Membrane Code: A Carrier of Essential Biological Information That Is Not Specified by DNA and Is Inherited Apart from It

The NatA Acetyltransferase Couples Sup35 Prion Complexes to the [PSI+] Phenotype

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The NatA Acetyltransferase Couples Sup35 Prion Complexes to the [PSI⁺] Phenotype